Ketamine

Migraine Case Report

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A 65 year old man reported 20 years of constant daily migraine without aura, with nausea, photophonophobia, triggered by barometric changes. Zomig or Imitrex would dull the pain a bit but it was never gone. Oxycontin 50 mg daily 6 months of every year dulled the pain but the nausea of migraine still persisted. He would taper off the opioid every 6 months, enduring weeks of withdrawal symptoms. He had been seen by some of the foremost migraine specialists in the country, and saw other neurologists before seeing me a few months ago.

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We elected to trial ketamine in a nasal spray – it can also be given under the tongue.

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I had never been convinced ketamine would work for migraine and often refer migraineurs to migraine specialists who offer Botox. However, I was encouraged by the report of the UCLA migraine expert, Alan Rapoport, MD, President of the International Headache Society, that injections of ketamine given repeatedly IM in the office, help status migrainosis.

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The issue encountered with ketamine in treating this patient was side effects. Therefore, I asked him to lower the dose to a one that produces no side effects, repeat that lower dose 3 times per day for 2 or 3 days. That generally allows the body to develop tolerance to side effects so thereafter higher doses can be tested.

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Ketamine has no effect on pain, none whatsoever, until you reach your dose, that is different in everyone. The dose is idiosyncratic, it differs in everyone

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For pain, ketamine at an effective dose relieves pain in 10 to 15 minutes.

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He never reached an effective dose because of side effects. Instead, after a few weeks on a dose he could tolerate without side effects, migraine went into complete remission. Complete remission for months. For at least three months, he’s had no migraine. This is the first time in 20 years he has been headache free. Never free of migraine for even one day.

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Ketamine is a powerful glial modulator. It reduces pro-inflammatory cytokines in the CNS. We tried adding another glial modulator but in two or three days he developed a migraine, stopped the drug, and after another one or two migraines more, he has been migraine free for a few weeks since then.

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For now, he remains on ketamine three times a day and is now trying twice daily dosing.

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As always, in any patient on medication that could have potential organ toxicity or lead to addiction, I monitor blood and urine regularly.

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This is unique.

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For about 15 years, I have treated patients with ketamine daily for chronic pain, those who have failed all prior medications, procedures, pumps and spinal cord stimulators. But we have always stopped if failing to achieve relief. I have no one who continued sub-therapeutic doses for 4 weeks or more despite no effect. None. This man did and now has sustained complete remission with no side effects.

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Less is more.

Is that true for other forms of chronic pain?

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It is important not to lock onto one dose if less will work. If, as research shows, ketamine lowers inflammatory cytokines in brain and cord, then over time, we may need less to maintain effect. At this time, we are very slowly decreasing daily frequency, very slowly, over months, to avoid triggering recurrence.

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This site is not for email.

If any questions, please schedule an appointment with my office.

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Public Warning:

Ketamine is a controlled substance.

Administered improperly, or without the guidance of a qualified doctor,

Ketamine may cause injury or death.

No attempt should be made to use Ketamine

in the absence of counsel from a qualified doctor.

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“Off label” means ketamine is FDA approved for another purpose, decades ago it was approved for anesthesia. In qualified hands, ketamine is one of the safest medications we have in our formulary.

Criticism of the CDC Opioid Guidelines

This excellent journal is edited by the gifted, much loved, and opinionated Forrest Tennant, MD, who we like to count on for not holding back. I missed it in the brief look I did today – this is necessarily sober.

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[Emphasis mine]

The criticisms surround the CDC guideline’s low-quality evidence base, which excludes all data from studies investigating opioid efficacy recorded from 3 months to 1 year duration. This is a concerning omission, according to Daniel B. Carr, MD, President of the AAPM, because the guidelines are intended for treating pain that lasts longer than 3 months. By contrast, associations like the Food and Drug Administration (FDA) do accept studies in this longer range.

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AAPM Response

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In a statement released by AAPM, the association said they cautiously support the efforts of the CDC to address the challenges that often accompany prescribing opioids for chronic non-cancer pain.

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“We know that doctors—primary care and pain medicine specialists—are integral in treating pain wisely and carefully monitoring for signs of substance abuse. Abuse and diversion of prescription opioids must be addressed,” said Dr. Carr, Professor of Public Health and Community Medicine at Tufts University. “Opioids are not the usual first choice for treating chronic non-cancer pain, but they are an important option—as part of a comprehensive multidisciplinary approach— that must remain available to physicians and appropriately selected patients.”

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Dr. Carr said that society needs to address both chronic pain and its treatment as public health challenges. This view is endorsed by the National Academy of Medicine and outlined in the draft National Pain Strategy from the NIH.

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[emphasis mine]

“Public health problems are typically complex; well-meaning, but narrowly targeted, interventions often provoke unanticipated consequences,” he said. “We share concerns voiced by patient and professional groups, and other Federal agencies, that the CDC guideline makes disproportionately strong recommendations based upon a narrowly selected portion of the available clinical evidence. It is incumbent upon us all to monitor the deployment of the guideline to ensure that it does not inadvertently encourage under-treatment, marginalization, and stigmatization of the many patients with chronic pain that are using opioids appropriately.

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“While we are largely supportive of the guidelines, we remain concerned about the evidence base informing some of the recommendations, conflicts with existing state laws and product labeling, and possible unintended consequences associated with implementation, which includes access and insurance coverage limitations for non-pharmacologic treatments, especially comprehensive care, and the potential effects of strict dosage and duration limits on patient care,” said Patrice A. Harris, MD, the AMA board chair-elect and chair of the AMA Task Force to Reduce Opioid Abuse.

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“We know this is a difficult issue that doesn’t have easy solutions and if these guidelines help reduce the deaths resulting from opioids, they will prove to be valuable. If they produce unintended consequences, we will need to mitigate them. They are not the final word. More needs to be done, and we plan to continue working at the state and federal level to engage policy makers to take steps that will help end this epidemic.”

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Very sobering issues and too many deaths from opioid overdose. Whether alone, in combination with alcohol or other sedatives and sleeping pills, the focus is on opioid dosages.

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The fear is what the DEA will do in response to the guidelines. The immediate reality is that insurance formularies have changed in strange and unpredictable ways the last few months. As always, we may need to adjust dosing as patients age or illnesses enter into an evolving lifetime of care. Be prepared to change the dose, alert to doses that may be too high for their current medical condition, and always alert to opioid misuse, addiction, misjudgement, and mental health. Be wise and do the right thing.

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Suicide prevention

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Sometimes, depression isn’t even in the picture. In one study, 60 percent of college students who said they were thinking about ways to kill themselves tested negative for depression.

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“There are kids for whom it’s very difficult to predict suicide — there doesn’t seem to be that much that is wrong with them.

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Suicide can be a very impulsive act, especially among the young, and therefore difficult to predict.

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About 90 percent of the people who try suicide and live ultimately never die by suicide. If the people who died had not had easy access to lethal means, researchers like Dr. Miller reason, most would still be alive.

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“People think of suicide in this linear way, as if you get more and more depressed and go on to create a more specific plan,” Ms. Barber said.

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Dr. Igor Galynker, the director of the Family Center for Bipolar Disorder at Mount Sinai Beth Israel, noted that in one study, 60 percent of patients who died by suicide after their discharge from an acute care psychiatric unit were judged to be at low risk.

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“The assessments are not good,” he said. So Dr. Galynker and his colleagues are developing a novel suicide assessment to predict imminent risk, based upon new findings about the acute suicidal state.

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In fact, suicide is often a convergence of factors leading to a sudden, tragic event. In one study of people who survived a suicide attempt, almost half reported that the whole process, from the first suicidal thought to the final act, took 10 minutes or less.

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Among those who thought about it a little longer (say, for about an hour), more than three-quarters acted within 10 minutes once the decision was made.

Ken Baldwin, who jumped from the Golden Gate Bridge and lived, told reporters that he knew as soon as he had jumped that he had made a terrible mistake. He wanted to live. Mr. Baldwin was lucky.

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Ms. Barber tells another story: On a friend’s very first day as an emergency room physician, a patient was wheeled in, a young man who had shot himself in a suicide attempt. “He was begging the doctors to save him,” she said. But they could not.

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Addiction

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Let us never forget the curse of addiction, and the profound misunderstanding our leaders make: it is a medical condition, not a choice. The war on drugs must be transformed from militarization of addiction to medicalization of addiction. Like Canada, Portugal and some of the South American countries.

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opioid and heroin overdose deaths are preventable. The drug Naloxone, which blocks the effects of heroin, is a safe, inexpensive antidote when someone is available to administer it, as is the case at Insite.

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Coda

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After all this, it feels like we’ve advanced a long way into the 21st century. Old stuff does not work. There sure is a whole bunch of stuff that no longer works. Life happened, and moved along.

Marijuana, cannabis, is overlooked for pain control

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CBD – cannabidiol — is the immune/glial suppressor

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It is anti-inflammatory in brain and spinal cord

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Correction 3/28/16:

It is not legal to transport CBD to states where marijuana is illegal, though it has no psychoactive properties. This is explained in detail by two doctors who wrote in drugpolicy.org, March 2015. I recommend reading the article as it makes several important points.

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The cannabis plant, and everything in it, is illegal under federal law. And even in states where it is legal, it is not legal to ship cannabis products from state to state, or to leave the state with such a product.

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A recent study from Israel showed that CBD in its natural form as a whole plant extract is superior over a single, synthetic CBD compound for treating illness. The plant has continually outperformed synthetic versions in research studies.

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…There are many support groups for children with epilepsy whose parents are using medical cannabis, such as this forum run through the Epilepsy Foundation. Connecting with them can be a great resource for staying on top of the developments with CBD and the other therapeutic cannabinoids in the cannabis plant.

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Dr. Malik Burnett is a former surgeon and physician advocate. He also served as executive director of a medical marijuana nonprofit organization. Amanda Reiman, PhD, holds a doctorate in Social Welfare and teaches classes on drug policy at the University of California-Berkeley.

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Cannabis has been used for thousands of years. It has been in the U.S. pharmacopoeia since 1850. A medical textbook from the 1920’s lists medical uses for cannabis. A Mexican American grandfather on hospice in 1995, explained how cannabis had helped his arthritic joints decades before.

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When alcohol prohibition failed and was repealed in 1933, Harry J. Anslinger, head of the Federal Bureau of Narcotics from 1930 to 1962, created the word marihuana claiming it led to addiction, violence, overdosage. Anslinger used racist propaganda to instill fear in Americans that only Mexicans and Negros use cannabis which led to creation of the Marijuana Tax Act passed by congress in 1937. Not unlike the CDC Opioid Guideliness of March 2016, it was passed over the objections of the AMA.

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The American Medical Association (AMA) opposed the act because the tax was imposed on physicians prescribing cannabis, retail pharmacists selling cannabis, and medical cannabiscultivation/manufacturing. The AMA proposed that cannabis instead be added to the Harrison Narcotics Tax Act. The bill was passed over the last-minute objections of the American Medical Association. Dr. William Creighton Woodward, legislative counsel for the AMA objected to the bill on the grounds that the bill had been prepared in secret without giving proper time to prepare their opposition to the bill. He doubted their claims about marijuana addiction, violence, and overdosage; he further asserted that because the word Marijuana was largely unknown at the time, the medical profession did not realize they were losing cannabis. “Marijuana is not the correct term… Yet the burden of this bill is placed heavily on the doctors and pharmacists of this country.”

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Israel’s Professor Rafael Mechoulam is widely recognized for his work on cannabis over more than 40 years. He and his lab isolated and identified THC, CBD, cannabinoid receptors, endogenous cannabinoids – your brain makes two of them! Your body has more cannabinoid receptors than any other type. It was he who published 40 years ago that CBD controls certain types of epilepsy in children – and it was ignored until Dr. Sanjay Gupta publicized this in the last one or two years.

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Professor Mechoulam says CBD from the plant (the plant is illegal in the United States) outperforms synthetic CBD.

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However, standards for CBD products do not exist, assays may be unreliable, it may be extracted with harsh chemicals that are harmful to those who are ill, and FDA has warned against false claims of efficacy.

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Nevertheless, there are indications CBD may help pain. It has no psychoactive properties. It does not cause intoxication. There is no THC in it.

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CBD, Cannabidiol, is one of the 86 known cannabinoids in the cannabis plant that has 400 chemicals. In addition, the plant has perhaps 100 or 200 unique terpenes, also said to help symptoms.

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Topical CBD may help – keep that in mind when Blue Shield’s formulary offers only rectal suppository morphine (unless you wait days and hope they will approve a prior authorization).

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I received a note today about Colorado Hemp Farmers:

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a woman in her sixties suffering from sciatica who is having her nurse rub her back with a coconut oil extract of a specific strain of industrial hemp rich in CBD, but without significant THC. She reports that the pain alleviation is remarkable with the soothing extract, which she judged to be superior to when commercially available CBD oil was used.

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Have any readers have tried CBD for pain?

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Your feedback would help to inform researchers to add an additional arm to the tests now being done in rats.

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I have heard from one man with severe pain today. He uses CBD in many forms. It helps pain a little, and also it is calming. He describes it like you know pain is better after you take ibuprofen. Similar with CBD. He does not feel at all drugged.

Doesn’t look too different from the opioid reduction strategy.

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But alternatives are unrealistic for some. Physical therapy is too expensive for Ms. Kubicka-Welander: she can scarcely make the rent on her home in a trailer court. Patients with a compromised liver cannot take high doses of acetaminophen. Those on blood-thinners should not use ibuprofen.

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I would add that the American Pain Society cautions against use of ibuprofen and similar NSAIDS in seniors. The risk of taking these drugs – GI bleed, heart attacks and arrhythmias – increases with age.

Here is a link to the formulary for long acting opioids for Blue Shield. You can see the update date on the bottom as 3/3/16. I could have added that they index rectal suppository Morphine as a Long Acting* Opioid as well: